tbuckley/cabot-search huggingface dataset:
Implications of ethnicity among patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (nivo/ipi).
Authors: Sally Leong, Sana Ali, Zeynep Busra Zengin, Luis A Meza, Nazli Dizman, Hedyeh Ebrahimi, Ameish Govindarajan, Daniela V. Castro, Xiaochen Li, Tane Kim, Sam Melamed, Mykola Onyshchenko, Sumanta Monty Pal, Alex Chehrazi-Raffle
Journal: Journal of Clinical Oncology (2023)

613 Background: Existing literature has reported differences in clinical outcomes by ethnicity in patients receiving immune checkpoint inhibitors (Olsen et al Front Oncol 2021). We investigated real-world outcomes between Latinx and non-Latinx mRCC patients treated with first-line nivo/ipi within a safety-net healthcare system and at a tertiary care center in Southern California. Methods: We performed a retrospective analysis of mRCC patients who received nivo/ipi within the Los Angeles County Department of Health Services (DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between Jan. 1, 2015 and Dec. 31, 2021. Patients were identified using institutional databases and clinical data were compiled from electronic health records. Patients with pathologic diagnosis of mRCC, age &gt; 18 years and receipt of nivo/ipi as first-line therapy were included. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards model with adjustments for other covariates. Results: Of 94 patients, 66 (70%) were male, 90 (94%) had clear-cell histology, and 87 (93%) had IMDC intermediate/poor risk disease. Forty patients (43%) were Latinx. Fifty (53%) and 44 (47%) patients received their care at a tertiary care center and within a safety-net healthcare system, respectively. Most Latinx patients (95%) were treated at DHS, and most non-Latinx patients (89%) were treated at COH. Latinx patients were significantly older than non-Latinx patients (59.5 vs 55 years, p=0.008). IMDC risk classification, body mass index, history of nephrectomy, and number of comorbidities were similar between both groups. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs 25.2 months, HR 3.61, 95% CI 1.96-6.66, p= &lt;0.01). Adjusting for age, gender, IMDC risk classification, history of nephrectomy, and number of co-morbidities, multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; p=0.01). At a median follow up of 11.0 months, the median OS was not met in either arm at the time of data cutoff (NR vs. NR, HR 1.34, 95% CI 0.44-4.11). Conclusions: Compared to non-Latinx patients,Latinx patients demonstrated shorter PFS; no difference was observed in OS although these data were immature. As the majority of Latinx patients received their care at DHS, our data suggest that disparities in access to care may significantly contribute to differences in clinical outcomes of mRCC patients receiving nivo/ipi.
The natural progression of patients with an IsoPSA value and its predictive ability of clinically significant prostate cancer on biopsy.
Authors: Nour Abdallah, Tarik Benidir, Zaeem M Lone, Ao Zhang, Andrew Wood, Caleb Curry, Samuel Haywood, Jihad Kaouk, Robert Abouassaly, Eric A. Klein, Christopher J. Weight
Journal: Journal of Clinical Oncology (2023)

325 Background: IsoPSA is a structure-based serum assay exploring the spectrum of possible prostate-specific antigen (PSA) isoforms. It was shown to outperform total and percent-free PSA in detecting clinically significant prostate cancer (csPCa) (grade group (GG) ≥2 on biopsy). IsoPSA reduced unnecessary biopsies and magnetic resonance imaging (MRI). We sought to compare the outcomes of eventual biopsy and imaging of surveilled patients with an initially normal or high IsoPSA, thus assessing IsoPSA’s prospective predictive ability of csPCa. Methods: We performed a single-center retrospective review of patients who underwent IsoPSA testing from 2017-present. Data was dichotomized into patients with normal (≤6) and high IsoPSA (&gt;6). We collected the outcomes of any consequent IsoPSA and PSA test, prostate biopsy and MRI. We calculated the statistical IsoPSA’s characteristics for the prediction of csPCa on biopsy. Results: The median follow-up time of 811 patients who underwent IsoPSA testing was 18 months (IQR, 16.5-20). Among 443 patients with initial low IsoPSA, 5 (1.1%) had a csPCa on a subsequent biopsy, 19 (4.3%) subsequent high IsoPSA, 122 (27.5%) rising PSA, and 22 (5%) csPCa on MRI. Among 368 patients with initial high IsoPSA, 105 (28.5%) had a csPCa on a subsequent biopsy and 106 (28.8%) on an MRI. The sensitivity of IsoPSA to predict csPCa was 95.5%, and the NPV was 94.8%. Among 124 patients with high IsoPSA and initial negative biopsy, 110 had a subsequent negative and 14 a positive biopsy (10GG1 (8.1%), 4 ≥GG2 (3.2%)), with a respective median IsoPSA of 7.2 and 9.6 (p=0.007). An IsoPSA&gt;10 generated an OR of csPCa of 7.2 (95%CI 2.1-25.2, p=0.0005). Conclusions: In 18-month follow-up, 1.1% of patients with normal IsoPSA developed csPCa compared to 28.5% of patients with high IsoPSA. In the cohort of patients with high IsoPSA and initially negative biopsy, 3.2% eventually developed csPCa, however, having a significantly higher IsoPSA than those who remained negative. The odds of having csPCa were 7 times higher with IsoPSA&gt;10. [Table: see text]
A phase III randomized trial of eribulin (E) with or without gemcitabine vs standard of care (SOC) for metastatic urothelial carcinoma (UC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937.
Authors: Sarmad Sadeghi, Melissa Plets, Primo N Lara, Catherine Tangen, Rick Bangs, Seth P. Lerner, Thomas W. Flaig, Daniel P. Petrylak, Ian M Thompson
Journal: Journal of Clinical Oncology (2023)

TPS581 Background: UC is 2nd most common genitourinary cancer. Current SOC offers platinum-based (PB) first line chemotherapy (chemo) with ddMVAC or gemcitabine-cisplatin (GC) regimens. For cisplatin ineligible patients (pts), SOC includes gemcitabine-carboplatin (GCa), and in select pts pembrolizumab. Erdafitinib is approved for pts with FGFR alterations and Enfortumab vedotin (EV) is approved for previously treated pts. A phase I/II CTEP study of eribulin (E) for metastatic UC (mUC) established the activity of E in UC with objective response rate (ORR) of 37.5% and a median progression free survival (PFS) of 4.1 months (mo) and median overall survival (OS) of 9.5 mo (N=150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed an ORR of 50%, median OS of 11.9 mo and median PFS of 5.3 mo (N=24). The most common Grade 3-4 toxicities included: neutropenia 63%, anemia and fatigue 29%. Pts with liver metastases benefited from therapy with 5 responders in 7 pts for GE vs 12 out 49 E. Methods: This is a phase III, randomized 3 arm study comparing E vs. GE vs. SOC (docetaxel, paclitaxel, or gemcitabine). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle. In the GE arm, gemcitabine is added to E at 1000 mg/m2 dose to D1 and D8. SOC follows standard dosing of the agents. There is no limit to the number/sequence of prior regimens. A simplified summary of eligibility criteria is presented here. All pts must have: received frontline systemic treatment such as PB chemo or a non-platinum regimen; received PD1/PDL1 Ab or be deemed ineligible for PD1/PDL1 Ab; received EV. Assuming a median OS for the SOC arm of 7 mo the study seeks to find at least a 50% increase in median OS to 10.5 mo (Hazard Ratio (HR) = 0.667). One-sided 0.0125 type I error to account for testing of two primary hypotheses (Each arm vs. SOC). 87% power to detect a 3.5 mo improvement in OS. We require 140 eligible (155 total) pts in each arm for a total of 465. The study was activated in Feb 2021 and accrual is ongoing. Funding: National Institutes of Health/National Cancer Institute grants U10CA180888, U10CA180819. Clinical trial information: NCT04579224 .
Factors related to men’s experience with prostate cancer germline testing.
Authors: Veda N. Giri, Laura Gross, Rebecca Hartman, Amy Leader, Young E. Whang, Anna Couvillon, Heather H. Cheng, Channing Judith Paller, Stacy Loeb, Lawrence Ivan Karsh, Sue J. Friedman, Tomasz M. Beer, Alexandra Sokolova, Scott W. Keith
Journal: Journal of Clinical Oncology (2023)

128 Background: Indications for prostate cancer (PCA) germline testing (GT) have greatly expanded, with genetics delivery being implemented in a variety of ways. Here we evaluate factors related to men’s experience with genetic evaluation (GE) in the PCA Genetic Risk, Experience, and Support Study – PROGRESS Registry. Methods: Men took online surveys that covered demographics, PCA history, mode of GE, and measures of patient-reported outcomes (PROs) (satisfaction [Demarco 2004] [Score 6-30; higher=greater satisfaction], decisional conflict [O’Connor 1995] [Score 16-80; higher=greater conflict], attitude re: GT [Marteau 2001] [Score 1-7; higher=perceived benefit], and knowledge of cancer genetics [Erblich 2005] [% correct of 15 questions]). Data were summarized using descriptive statistics. Multiple linear regression modeling assessed relationships between characteristics, mode of GE, and PROs. Significance level was a nominal α = 0.05 (SAS v9.4). Results: PROGRESS reached accrual goal (n=500). Characteristics (among n=414): 87.7% White, 6.0% Asian, 87.7% bachelor’s degree or higher. Among n=422, 46.9% reported PCA diagnosis. Among n=416 who reported genetic results, 27.9% had pathogenic/likely pathogenic variants (P/LPV), 14.7% had VUS, and 9.9% did not know. Mode of GE was delivered: by genetics professional (GP) (24.9% in-person,10.5% phone, 6% telehealth), by doctor (21.1%), from website (20.8%), by genetics lab (5%), and by video (10.8%). Some reported not having pretest discussion (23.7%) or not knowing (8.1%). From multiple regression models, several factors including race, mode of GE, education, and genetic results were related to PROs. Conclusions: Several factors may impact men’s experience with PCA GE, deserving further study into root causes particularly related to diverse populations and genetics care delivery models to support men and their families. [Table: see text]
Cabozantinib in the elderly with metastatic renal cell carcinoma undergoing geriatric G8 screening test: A prospective multicenter observational study (ZEBRA/MEET-URO 9).
Authors: Umberto Basso, Sebastiano Buti, Elena Verzoni, Mariella Sorarù, Marilena Di Napoli, Lucia Fratino, Daniele Santini, Francesco Grillone, Vincenzo Emanuele Emanuele Chiuri, Claudia Carella, Francesco Atzori, Giandomenico Roviello, Donata Sartori, Marco Maruzzo, Francesco Pierantoni, Melissa Bersanelli, Melissa Ballestrin, Chiara De Toni, Alvise Mattana, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2023)

647 Background: Cabozantinib (CABO) is an oral tyrosine kinase inhibitor registered for the treatment of metastatic renal cell carcinoma (mRCC) for the first or subsequent lines. Tolerability in real world elderly patients is poorly documented. G8 is a short test for vulnerability gaining increased interest as a screening tool for trials in geriatric oncology. Methods: ZEBRA/MEET-URO 9 was a prospective multicenter study of safety and activity of CABO administered to pts ≥70 years with mRCC, either in the first or subsequent lines of treatment, until progression or unacceptable toxicity. All pts underwent G8 score at baseline, with a cut-off for vulnerability of 14 or below. Data on tolerability and activity were collected prospectively after signature of informed consent. Results: A total of 104 pts started CABO at 13 Italian Centers, 38,5% as first line. Median age was 75.8 yrs (range 70.2-87.4 yrs, 26 pts ≥80 yrs), 73.1% males. IMDC score was good 19.2%, intermediate 53.9%, poor 26.9%. Primary tumor had been removed in 82.7% of pts, histology was clear cell 78.8%, papillary 8.7%, chromophobe 5.8%, unclassified 6.7%. G8 score was ≤14 in 65.4% of pts. Up-front dose reduction of CABO was more frequent in pts with low G8 score (79.4 vs 41.7%, p=0.003), but eventually the majority of pts (91.4%) underwent dose reductions of CABO. After a median treatment of 6.4 months (0.5-26.1 months), 38.4% of pts developed G3-4 toxicities, 22.1% interrupted treatment due to adverse events, 2.8% (3 pts) died due to cardiovascular or thromboembolic events. Median PFS was 7.6 months (95% CI=5.8-12.6 months) in first line, 10.0 months (5.8-15.6) in second or further lines, median OS was 20.1 months (11.1-not reached) and 15.6 months (12.5-not reached), respectively. G8 score ≤14 did not correlate with rate of temporary interruptions &gt;7 days, hospitalization, incidence of G3-5 toxicities, as well as with PFS. Pts with G8 score ≤14 had a trend for reduced OS, but difference was not statistically significant both in the first and further lines of treatment. Conclusions: Screening G8 test was positive in more than a half of pts, underlying the need for detailed geriatric assessment and increased clinical monitoring of such patients. A G8 score ≤14 correlated with up-front dose reduction of CABO but not with G3-5 toxicities probably due to the high rates of dose reductions in the whole cohort. Correlation between low G8 score and OS could not be demonstrated in this population.
Genomic alterations in patients with prostate cancer with liver metastases.
Authors: Crystal Casado, Sydney Caputo, Ellen B. Jaeger, Albert Jang, Patrick L Sweeney, Sree M Lanka, Kanika Gupta, Olivia Pocha, Maddie Hawkins, Minqi Huang, Alexandra Lieberman, Jennifer Schwartz, Patrick Miller, Pedro C. Barata, Jodi Lyn Layton, Brian E. Lewis, Elisa M. Ledet, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2023)

248 Background: mCRPC patients with liver metastases have a poor prognosis and often progress rapidly on a variety of treatments. Previously, preliminary ctDNA analyses of mCRPC patients with liver metastases showed a range of commonly altered genes in patients with liver metastases (Ranasinghe et al; 2019). In this follow-up, we evaluated ctDNA alterations in an expanded cohort of mCRPC patients with liver metastases. Methods: From Tulane Cancer Center, retrospective review of mCRPC patients was used to identify patients with confirmed liver metastasis. All liver metastases were confirmed based on imaging data. All patients included had ctDNA evaluated with a multi-gene cancer panel via Guardant 360 assay (Guardant Health, Inc). Additional clinical annotation including family history, germline testing, staging, imaging, and laboratory values. Statistical analyses were performed with Fisher’s Exact and Wilcoxon Rank Sum tests. Results: 158 mCRPC patients with appropriate diagnostic imaging as well as ctDNA testing. From this group, 8% (n= 12) had confirmed liver metastases. Among the patients with liver metastasis, the most common alterations detected were in AR (50%; 6/12) and PIK3CA (25%; 3/12). Patients with liver metastasis were more likely to have amplifications in FGFR1 detected in their ctDNA (OR= 14.40; 95% C.I. (1.83, 113.22); p= 0.03). In addition to ctDNA, germline data was assessed, and it was found that patients with liver metastasis were more likely to have a pathogenic germline mutation (OR= 7.61; 95% C.I. (2.85, 20.31); p&lt;.0001). The most common germline mutations detected in patients with liver metastasis were in BRCA2 (n= 3) and TP53 (n= 2). Conclusions: Though liver metastasis are less common in prostate cancer, it often occurs following extensive treatment and results in a poor prognosis for patients. In patients with liver metastasis, FGFR1 amplification was more often detected in ctDNA. Importantly, patients with liver metastasis were significantly more likely to have a pathogenic germline alteration.
Awareness of genetic risk for prostate cancer (PCa) in men from families with germline mutations in DNA-repair genes.
Authors: Massimo Lazzeri, Vittorio Fasulo, NicolòMaria Buffi, Giovanni Lughezzani, Paolo Casale, Alessio Benetti, Alberto Saita, Rodolfo Hurle, Giorgio Ferruccio Guazzoni, Giuseppe Chiarelli, Rosanna Asselta, Giulia Soldà
Journal: Journal of Clinical Oncology (2023)

328 Background: Although one of the most important risk factors for prostate cancer (PCa) is a family history of the disease, there is a poor awareness of genetic risk. The aim of the current study is to investigate the awareness of genetic risk for PCa in men belonging to female families with germline variants in DNA-repair genes (DRGs). Methods: Data were extracted by a prospective observational study designed to select men with germline pathogenic variants (PVs) and offer them a dedicated PCa screening. The selection of probands was performed by genetic counseling and testing of male grade I relatives of female patients with a PVs. Male candidates were identified after reviewing the genealogical trees of all women who had received the diagnosis of breast and/or ovarian cancer and tested positive for a PVs. All the probands, 35-69 yrs old, who resulted positive for PVs were offered to participate to a specific PCa screening based on annually digital rectal examination (DRE), detection of PHI, which is a blood test including total PSA, free PSA, free/total PSA and -2proPSA, and multiparametric MRI. The primary outcome was the “willing to be tested”, defined as a proxy for male awareness of PCa risk. The secondary endpoint was the acceptance rate to be screened. Results: We reviewed the genealogical trees of breast/ovarian cancer female patients from January 2017 to December 2021 and we identified, over 1256 families, 139 positive cases for PVs in DRGs. Among 139 families, we identified 378 “healthy” 35-69 yrs old men, who were offered a genetic counseling, and if they agree a genetic testing. Overall 117/378 (31%) healthy males declared to be interested to be tested. Out of the 51 new tests (66 men already tested out of the study), we found 30 (58.8%) positive men. All the new positive tested men accepted to attend the PCa screening. Living in Northern Italy, having at least one child and higher (degree) level of education were the strongest predictors of willing for testing (p&lt;0.01). Conclusions: Our data reveals a limited will to be tested, but all men tested positive for PVs accepted to participate to the PCa screening. These findings strongly support the urgent need to implement awareness of genetic risk for PCa.
Patient perceptions regarding the process of obtaining oral prostate cancer medications.
Authors: Eric B Schwartz, Allison Furgal, Gina Widmer, Megan Veresh Caram, Christine M Veenstra
Journal: Journal of Clinical Oncology (2023)

120 Background: Various oral therapies exist and have improved outcomes for men with prostate cancer. These agents are expensive and put patients at risk for financial toxicity. Although assistance mechanisms exist to offset these costs, navigating through assistance can be complicated and places excess burdens on patients. We conducted a survey of men prescribed oral therapies for prostate cancer to assess financial toxicity and perceptions on the process of obtaining oral cancer medications for prostate cancer. Methods: Patients with prostate cancer who had been prescribed abiraterone, enzalutamide, apalutamide or darolutamide at our institution in the six months prior to survey distribution were identified. Those with an email address were eligible for inclusion and sent a survey. Financial toxicity was assessed using the FACIT-COST score. Perceptions of the process of obtaining medication were assessed with a novel measure, which included questions regarding affordability, delays in care and ease of obtaining medications. We assessed bivariate associations between financial variables and financial toxicity measures. Results: Of 238 patients identified, 188 had a listed email address. Response rate was 28% of eligible patients (n = 53). Among respondents, 53% reported household income &lt; $100,000 and 32% &gt; $100,000, 15% declined to answer. A total of 41% utilized commercial insurance, 23% Medicare D, 28% an alternative Medicare program, 2% Medicaid and 4% had no prescription coverage. Monthly costs were between $100 and $1000 for 15% of patients and &gt; $1000 for 6%. A total of 25% of patients considered their medication somewhat or very unaffordable; 13% were somewhat or not at all confident about affording their medication in the future; 6% reported delays in starting; 15% found the initial process of obtaining their medication somewhat or very stressful; 9% reported ongoing stress about affording their medications. Those with monthly cost &gt; $100 were less likely to consider their medication affordable (p = 0.001). Those with commercial insurance were least likely to perceive delays in care (p = 0.024). Primary insurance type but no other variable was associated with difference in COST score with those who had commercial insurance reporting less financial toxicity than those with Medicare. Conclusions: The costs of oral prostate cancer medications are a concern for many men with prostate cancer. In a survey at our institution, many patients have high costs, despite the availability of financial assistance. In addition, many reported distress and uncertainty related to the process of obtaining their prostate cancer medications. Our survey was limited by small sample size and low response rate utilizing email as primary contact. We expect that many patients without access to email would be those at higher risk of financial toxicity. Further studies will aim to recruit patients directly in clinics.
Metformin for biochemical recurrence of prostate cancer: Immune data from a phase 2 study.
Authors: Marijo Bilusic, NIcole J Toney, Renee Nicole Donahue, Fatima Karzai, Ravi Amrit Madan, Jeffrey Schlom, James L. Gulley, Priyamvada Rai, Cassie Due, Philip Gregory, Beatriz Mateo-Victoriano, Elizabeth R. Plimack, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2023)

377 Background: Metformin impacts immune response in several ways. It protects CD8 TILs from apoptotic death, downregulates CD39 and CD73, reduces MDSC activity and suppresses the transcription of PD1 thus enhancing CD8+ T cell antitumor activity (Ma et al, 2000, Nature). There is limited data on the immunologic impact of metformin treatment in hormone sensitive prostate cancer. Methods: We conducted an open label, randomized, phase II trial of bicalutamide with or without metformin of patients with high risk, biochemically recurrent prostate cancer (NCT02614859). Patients were randomized 1:2 to observation for an initial 8 weeks or metformin 1000 mg twice daily. Bicalutamide 50 mg/day was added after 8 weeks to both arms. The study discontinued accrual after interim analysis indicated no difference in PSA at 32 weeks between the two arms; however, metformin monotherapy for 8 weeks induced modest PSA declines observed in 40% of patients. Here we report immune responses in a subgroup of patients (N=12), including systemic cytokine levels and 158 circulating immune cell subsets after 8 weeks of metformin monotherapy. Results: Twelve patients treated at the NCI were analyzed. After 8 weeks, the metformin arm showed increased pDCs and lower Tregs compared to baseline. Significant differences in the percent change of immune parameters after 8 weeks of metformin monotherapy compared to 8 weeks of observation are summarized. Conclusions: Metformin has been shown to reduce markers of immune exhaustion in hormone sensitive prostate cancer which is supported by a greater reduction of PD-1 + and Tim3 + NK cells. Additional immune changes included increases in activated subpopulations of natural killer (NK) cells, which have been reported as a potential predictive biomarker of prolonged treatment response to hormone therapy in prostate cancer (Pasero et al, Oncotarget, 2015). Clinical trial information: NCT02614859 . [Table: see text]